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Adjuvant Vaccine Development

During the 1990’s, we developed a composite material that resulted in a new class of antimicrobial agents with activity against gram–positive bacteria and spores, fungi and viruses.  These nanoemulsions are oil-in-water, nanoscale (< 600 nm) emulsions formulated with surfactants.  Additional studies demonstrated that nanoemulsions are not only effective antimicrobials but potential intranasal vaccine adjuvants as well.  The technology was licensed to NanoBio Corp. in 2000 for commercialization and is still a major scientific focus for the Institute. 

Nanoemulsions as a Mucosal Vaccine Adjuvant

While originally developed as microbicidal agents, studies fortuitously demonstrated that nanoemulsions are a promising new type of adjuvant for nasopharyngeal vaccines.  Work was being performed to show that placing nanoemulsion into the nares of mice could protect them from subsequent respiratory challenge with an LD90 of Influenza virus.  The mice were successfully protected from challenge even two hours after the material was placed into the nares.  However, when challenged with live virus three weeks later, the same animals were protected from Influenza pneumonitis without nanoemulsion prophylaxis, and were shown to have high titers of anti-influenza antibodies.  Subsequent studies documented that placing Influenza virus in the nares with nanoemulsion on only a single occasion produced strong protective immunity. (Myc A, Kukowska-Latallo JF, Bielinska AU, Cao P, Myc PP, Janczak K, Sturm T, Grabinski MS, Young K, Chang J, Hamouda T, Olszewski MA and Baker JR, Jr: Development of immune response that protects mice from viral pneumonitis after a single intranasal immunization with influenza A virus and nanoemulsion. Vaccine 21(25-26); 2003, 3801-3814).

Figure 1: Intranasal vaccination of animals with a virus / nanoemulsion mixture induced high levels of anti-influenza A, Ann Arbor strain. IgG.

Mice were vaccinated one time with nanoemulsion alone, formaldehyde-killed virus, formaldehyde-killed virus-nanoemulsion, or virus/nanoemulsion mixture. Sera were collected on day 20 of the experiment for the assessment of IgG. Antibodies levels were expressed as an index of the geometric mean +/- SD for each experimental group. P-value was calculated using Student's t-test with C-Cochran and Cox correction. Symbol (*) depicts significance (P< 0.05) between animals vaccinated with formaldehyde-killed virus/nanoemulsion versus animals vaccinated with virus/nanoemulsion.

Mice immunized intranasally with the virus/nanoemulsion mixture did not show signs of illness, and their core body temperatures were within normal range for 14 days. Moreover, the lungs of immunized animals appeared grossly normal, and histological examination showed no indication of influenza pneumonitis or upper airway inflammation. These results show that nanoemulsions can inactivate virus without causing upper or lower airway mucosal toxicity in treated animals.

Mechanism of Action of Nanoemulsion Vaccine

Graphic design by Paul D. Trombley, adapted from earlier work by Holly R. Fischer, MFA.

Figure 2: Mechanism of Action of Nanoemulsion Vaccine
A. Nasal spray nanoemulsion vaccine fuses with antigen and is then sprayed into a nostril.
B. Nanoemulsion droplets with antigen penetrate the nasal mucosa.
C. Diagram of nanoemulsion droplet with antigen in its interface. Blue dots are antigen present in emulsion.
D. Antigen delivery by nanoemulsion into nasal submucosa where fusion with dendritic cells delivers the antigen to the immune system. Dendritic cells can then transport the antigen to other parts of the body to trigger the desired immune response.

As current approaches to vaccination for a number of viral agents have drawbacks due to the use of live virus, complex vaccination protocols or the addition of adjuvants unacceptable for humans, we have continued our determination whether mixing nanoemulsion with specific viral agents will provide a rapid and effective means for a killed virus vaccine for certain viral agents.

Instead of virus, we have also used purified recombinant proteins placed in the nanoemulsion to document that this mixture induced mucosal immunity and systemic TH1 responses.   This was of interest, as there was no toxin or other component other than the nanoemulsion (diluted 100 fold in saline) and the recombinant protein antigen.  Given the safety profile of the nanoemulsion, these findings supported the further investigation of nanoemulsions as clinically useful nasopharyngeal adjuvants for humans. 

MNiMBs has been fortunate to be well funded in pursuing nanoemulsions as a mucosal vaccine adjuvant.  MNiMBS Scientists are currently funded to pursue nanoemulsion based vaccines for:

Click each link for more details on specific vaccines being developed.

We have promising results for an HIV adjuvant vaccine.

MNiMBs is also in the process of developing programs for:

  • HIV
  • Dengue
  • RSV
  • H5N1
  • Respiratory corona viruses

To learn more about nanoemulsions click here MNiMBS welcomes collaborative partners and encourages communication between groups.  Those people interested in collaborating are encouraged to contact MINanotech@umich.edu for further discussion.

Nanoemulsion

 

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